title: Conformation-dependent DNA damage induced by gold nanoparticles.
abstract: The sensitivity of two conformations of plasmid DNA, the A and B forms, to strand break formation induced by gold nanoparticles (GNPs) is investigated by varying the GNP to DNA ratio in solution and the degree of DNA hydration. Decreasing DNA hydration via lyophilisation or by replacement of water with ethanol in solution modifies its conformation from the B to the A form. The yields of single strand breaks (SSB) are found to be highly dependent on the amount of DNA in the A configuration. The damage also increases with the amount of GNPs bound to DNA. At a ratio of two GNPs for one plasmid in an 80%-ethanol, 20%-water solution, 50% of the initial supercoiled population is converted to SSB. Thus, close contact with GNPs causes extensive damage to DNA in the A form. Since during transcription the DNA-RNA duplexes adopt an A form, GNPs could be genotoxic. Our results suggest that GNPs may have potential as chemotherapeutic agents if conjugated to nuclear targeting ligands. Considering their additional radiotherapeutic properties, targeted GNPs could also become highly effective in the treatment of cancer with concomitant chemoradiation therapy.
authors.affiliation: Fujian Provincial Key Laboratory of Photocatalysis-State Key Laboratory Breeding Base, College of Chemistry and Chemical Engineering, Research Institute of Photocatalysis, Fuzhou University, Fuzhou 350002, PR China.
authors.forename: Chuanna
authors.initials: C
authors.lastname: Huang
authors.forename: Qianhong
authors.initials: Q
authors.lastname: Bao
authors.forename: Darel
authors.initials: D
authors.lastname: Hunting
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Léon
authors.initials: L
authors.lastname: Sanche
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D018736:DNA Adducts / Q000737:chemistry / Q000187:drug effects; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006046:Gold / Q000494:pharmacology*; D006801:Humans; D053768:Metal Nanoparticles; D046529:Microscopy, Electron, Transmission; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D018736:DNA Adducts; D004277:DNA, Single-Stranded; D006046:Gold